Allosteric transition

In 1965, Jacques Monod, Jeffries Wyman, and Jean-Pierre Changeux proposed a theoretical model of allosteric transitions based on the observation that allosteric proteins are oligomers. They suggested that allosteric proteins can exist in (at least) two conformational states, designated R, signifying relaxed, and T, or taut, and that, in each protein molecule, all of the subunits have the same conformation (either R or T). That is, molecular symmetry is conserved. Molecules of mixed conformation (having subunits of both R and T states) are not allowed by this model. 

FIGURE 15.9 Monod-Wyman-Changeux (MWC) model for allosteric transitions. Consider a dimeric protein that can exist in either of two conformational states, R or T. Each subunit in the dimer has a binding site for substrate S and an allosteric effector site, F. The promoters are symmetrically related to one another in the protein, and symmetry is conserved regardless of the conformational state of the protein. The different states of the protein, with or without bound ligand, are linked to one another through the various equilibria. Thus, the relative population of protein molecules in the R or T state is a function of these equilibria and the concentration of the various ligands, substrate (S), and effectors (which bind at f- or Fj ). As [S] is increased, the T/R equilibrium shifts in favor of an increased proportion of R-conformers in the total population (that is, more protein molecules in the R conformational state). 

Glycogen phosphorylase conforms to the Monod-Wyman-Changeux model of allosteric transitions, with the active form of the enzyme designated the R state and the inactive form denoted as the T state (Figure 15.17). Thus, AMP promotes the conversion to the active R state, whereas ATP, glucose-6-P, and caffeine favor conversion to the inactive T state. 

Monod J, Wyman J, Changeux J-P. On the nature of allosteric transitions a plausible model. J Mol Biol 1965 12 88-118. 

To describe the all-or-none transition between distinct conformational states of enzymes or receptors — an allosteric transition. In keeping with this usage, the constant that describes the position of the equilibrium between the states (e.g., E0 in the schemes of Figures 1.11 and 1.28) is sometimes described as the allosteric constant. 

K. L. Martinez, Y. Gohon, P.-J. Corringer, C. Tribet, F. Merola, J.-P. Changeux, J.-L. Popot (2002) Allosteric transitions of Torpedo acetylcholine receptor in lipids, detergent and amphipols molecular interactions vs. physical constraints. FEBSLett., 528 251-256... 

Allosteric Transitions of Secondary Structure Induced by Superhelical Stress... 

In the absence of chloroquine, the apparent torsion constants for supercoiled pBR322 DNAs with normal (secondary structure, so the secondary structures of supercoiled and linear DNAs might not be identical, despite their similar torsion constants. 

R. Negri, F. Delia Seta, E. di Mauro, and G. Camilloni, Topological evidence for allosteric transitions in DNA secondary structure, Biophys. J., submitted. 

Note that negative cooperativity cannot occur in the Monod-Wyman-Changeux allosteric transition model, because the dissociation constant is equivalent for all sites. Thus, positive cooperativity can only result in this binding mechanism as a consequence of the recruitment of binding sites from the T-state in an all-or-none transition to the R-state. Any occurrence of negative cooperativity can be regarded as prima facie evidence... 

Although the mechanism for phase II block is not completely understood, a series of allosteric transitions in the AChR is suspected. One model to describe this has the AChR in equilibrium among four conformations resting, active, inactive, and desensitized. Agonists stabilize the active and desensitized states, whereas antagonists tend to stabilize the resting and possibly the desensitized state. 

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